Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

FLOLAN (NDA-020444)

(EPOPROSTENOL SODIUM)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

08/24/2021 (SUPPL-25)

Approved Drug Label (PDF)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Newly added information:

FLOLAN prepared with pH 12 STERILE DILUENT for FLOLAN must not be used with any preparation or administration materials containing PET or PETG. Only use materials provided by a healthcare provider or pharmacist.

PATIENT INFORMATION

Additions and/or revisions underlined:

How should I use FLOLAN?

Removal of sterile diluent for FLOLAN (comes in a glass bottle) information

Before you use FLOLAN, you must mix (reconstitute) FLOLAN powder with pH 12 STERILE DILUENT for FLOLAN (comes in a plastic bottle).

Do not mix FLOLAN with any other diluent. You must use pH 12 STERILE DILUENT for FLOLAN.
FLOLAN prepared with pH 12 STERILE DILUENT for FLOLAN must not be used with any preparation or administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG). Only use materials provided by a healthcare provider or pharmacist.

12/12/2018 (SUPPL-24)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Post-Marketing Experience

Addition of the following:

Cardiac: High output cardiac failure (consider dose reduction)

10/23/2018 (SUPPL-23)

Approved Drug Label (PDF)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Newly added information:

FLOLAN prepared with pH 12 STERILE DILUENT for FLOLAN must not be used with any preparation or administration materials containing PET or PETG. Only use materials provided by a healthcare provider or pharmacist.

05/14/2018 (SUPPL-22)

Approved Drug Label (PDF)

5 Warnings and Precautions

(PLR conversion: subsections created as below, see label for complete information)

Pulmonary Edema
Rebound Pulmonary Hypertension following Abrupt Withdrawal
Vasodilation
Increased Risk for Bleeding

6 Adverse Reactions

6.2 Postmarketing Experience

(new subsection added)

The following events have been identified during postapproval use of FLOLAN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic

Anemia, hypersplenism, pancytopenia, splenomegaly, thrombocytopenia. Endocrine and Metabolic

Hyperthyroidism. Gastrointestinal Hepatic failure.

Respiratory, Thoracic, and Mediastinal Pulmonary embolism.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Limited published data from case series and case reports have not established an association with FLOLAN and major birth defects, miscarriage or adverse maternal or fetal outcomes when FLOLAN is used during pregnancy. There are risks to the mother and fetus from untreated pulmonary arterial hypertension (see Clinical Considerations). In animal reproduction studies, pregnant rats and rabbits received epoprostenol sodium during organogenesis at exposures of 2.5 and 4.8 times the maximum recommended human dose (MRHD), respectively, and there was no effect on the fetus (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death.

Data

Animal Data: Embryo-fetal development studies have been performed in rats and rabbits during organogenesis. Epoprostenol sodium doses up to 100 mcg/kg/day, a dose that was maternally toxic in rabbits but not in rats, (600 mcg/m2/day in rats, 2.5 times the MRHD, and 1,180 mcg/m2/day in rabbits, 4.8 times the MRHD based on body surface area), had no effect on the fetus.

In a postnatal development study, epoprostenol sodium was administered subcutaneously to female rats for 2 weeks prior to mating through weaning and to male rats for 60 days prior to and through mating at a male and female toxic dose of up to 100 mcg/kg/day (600 mcg/m2/day, 2.5 times the MRHD based on body surface area). There was no effect on growth and development of the offspring.

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of epoprostenol in either human or animal milk, the effects on the breastfed infant, or the effect on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FLOLAN and any potential adverse effects on the breastfed child from epoprostenol or from the underlying maternal condition.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(new subsection added)

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Advise patients:

FLOLAN must be reconstituted only with STERILE DILUENT for FLOLAN or pH 12 STERILE DILUENT for FLOLAN.
Reconstituted solution prepared with STERILE DILUENT for FLOLAN must be used with a cold pouch if not administered within 8 hours.
Reconstituted solutions prepared with pH 12 STERILE DILUENT for FLOLAN do NOT require use with a cold pouch.
FLOLAN is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump. Thus, therapy with FLOLAN requires commitment by the patient to drug reconstitution, drug administration, and care of the permanent central venous catheter. Patients must adhere to sterile technique in preparing the drug and in the care of the catheter, and even brief interruptions in the delivery of FLOLAN may result in rapid symptomatic deterioration. A patient’s decision to receive FLOLAN should be based upon the understanding that there is a high likelihood that therapy with FLOLAN will be needed for prolonged periods, possibly years. Consider the patient's ability to accept and care for a permanent intravenous catheter and infusion pump.
To adjust infusion rates of FLOLAN only under the direction of a physician.
To avoid interruptions in drug delivery, the patient should have access to a backup infusion pump and intravenous infusion sets.

To contact their healthcare providers if any unusual bruising or bleeding develops.

PATIENT INFORMATION

(extensive additions, please refer to label)

Other

(PLR conversion)